Adaptive Evolution Targets a piRNA Precursor Transcription Network

• Published in: Cell reports (Cambridge) 2020-02, Vol.30 (8), p.2672-2685.e5
• Main Authors: Parhad, Swapnil S., Yu, Tianxiong, Zhang, Gen, Rice, Nicholas P., Weng, Zhiping, Theurkauf, William E.
• Format: Article
• Language: English
• Subjects: adaptive evolution; Alleles; Animals; cross-species complementation; CtBP; Cutoff; DNA Transposable Elements - genetics; Drosophila - genetics; Drosophila Proteins - metabolism; Gene Regulatory Networks; Genes, Dominant; Models, Biological; Mutation - genetics; piRNA cluster transcriptional regulation; piRNA pathway; RNA, Small Interfering - metabolism; Transcription Factors - metabolism; Transcription, Genetic; transposon silencing; TRF2
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.01.109

In Drosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are bound by the Rhino-Deadlock-Cutoff complex. The HP1 homolog Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription from both genomic strands. Cuff function is less well understood, but this Rai1 homolog shows hallmarks of adaptive evolution, which can remodel functional interactions within host defense systems. Supporting this hypothesis, Drosophila simulans Cutoff is a dominant-negative allele when expressed in Drosophila melanogaster, in which it traps Deadlock, TRF2, and the conserved transcriptional co-repressor CtBP in stable complexes. Cutoff functions with Rhino and Deadlock to drive non-canonical transcription. In contrast, CtBP suppresses canonical transcription of transposons and promoters flanking the major germline clusters, and canonical transcription interferes with downstream non-canonical transcription and piRNA production. Adaptive evolution thus targets interactions among Cutoff, TRF2, and CtBP that balance canonical and non-canonical piRNA precursor transcription. [Display omitted] •Adaptive evolution produces a dominant-negative allele of the piRNA gene cuff•Cutoff balances interlinked canonical and non-canonical piRNA cluster transcription•CtBP suppresses canonical transcription of both piRNA clusters and transposons Parhad et al. use cross-species complementation to determine the functional impact of adaptive evolution. These studies show that adaptive evolution of the piRNA pathway protein Cutoff, which is required for transposon silencing and genome maintenance, targets interactions with conserved canonical and non-canonical transcription factors that regulate piRNA precursor expression.